Core B is an essential resource for the work of the Program Project as a whole. The core will provide all investigators in the program NOD mice which have been carefully bred and housed in a specific pathogen free environment to give a high incidence of diabetes - 90% in females and 65% in males by the age of 6 months. We have also developed a number of transgenic and gene knockout strains on the NOD genetic background by introgressively backcrossing these strains of mice to NOD core stock. In addition, some transgenic strains have been generated by direct injection of transgene DNA into the ova of NOD mice and in these strains, extensive backcrossing is not necessary. Finally he core also maintains congenic NOD strains that serve as controls for experiments that require NOD genetic background but different MHC as well as strains that can serve as controls for the NOD H-2. The NOD mouse core is routinely tested for the genetic integrity of the mice and in addition to generation of the NOD mutant mice by several generations of backcross to NOD, these mice are also tested for NOD background genes by PCR analysis of microsatellites for the 15 currently known NOC susceptibility loci. Mice at each successive backcross generation are selected for incorporation of the NOD susceptibility loci. Mice are housed in specific pathogen free microisolator cages and routinely monitored for pathogens by serology. The rooms in which mice for core B are housed are the cleanest in the Yale Immunobiology Mouse Unit. The core will provide NOD and NOD congenic mice for in vitro and in vivo experiments to all investigators int he program. In addition, the various NOD transgenic and gene knock-out animals provide new models of both accelerated disease and protection against diabetes which will also be available for study. Finally, the mice will serve as pancreatic islet donors for investigators and islet isolations will be performed in Core C. The availability of mice from Core B allows a constant supply of mice with known characteristics and obviates the need for purchase of mice with the attendant costs and risks to the health of the animals.